Lecture 12- Immune Responses To Infectious Diseases Flashcards
What are the 4 main types of pathogens that cause infectious diseases?
Viruses, bacteria, protozoa, and helminths.
What are the main steps needed in order for a microbe to establish infection?
- Penetrate epithelial barrier - not easy. 2. Compete with normal flora for binding sites. 3. Evade innate immunity.
What are the epithelial barriers that microbes must penetrate to establish disease?
Skin, GI lining, respiratory lining.
What are the components of innate immunity that microbes must evade in order to establish infection?
Macrophages, neutrophils, NK cells.
What is the physiological function of the host immune response?
Combat infections.
How are inherited and acquired immune deficiencies manifested?
By increased susceptibility to infection and activation of latent infections.
Defense against infections is mediated by what?
The early reactions of innate immunity and the later responses of adaptive immunity.
What characteristic of adaptive immunity helps to keep pace with rapidly dividing microbes that evade innate immunity?
Lymphocyte expansion.
What are better able to deal with diverse microbes?
Specialized immune responses.
Describe the evolutionary battle of microbes and hosts.
Microbes and their hosts are engaged in a constant struggle for survival.
The outcome of infections is determined by what?
The balance between host defenses and the ability of microbes to evade or resist immunity.
Immune responses to microbes are themselves capable of causing what?
Tissue injury.
What are the principal mechanisms of defense against microbes?
Antibodies, phagocytes, and T cells.
How do antibodies defend against microbes?
Block the infectivity of microbes; best way of preventing infection before it takes hold (goal of vx).
How do phagocytes defend against microbes?
Phagocytosis and intracellular killing of microbes by working with Ab’s and T cells.
How do T cells defend against microbes?
Kill infected cells when infection cannot be blocked, or cleared, by phagocytes.
Plasma cell = ___________ protection.
Rapid.
Memory B cells = ______________ protection.
Long-lived protection.
Describe the phase of immune responses of T cells.
Naive T cell –> sense a microbe –> effector T cells –> memory T cells.
What is the adaptive immune response of an extracellular microbe (bacteria, viruses)?
Endocytosed antigen stimulates CD4 helper T cells (Th1, Th17) –> antibody, inflammation.
What is the adaptive immune response of an intracellular microbe in phagocytes?
Antigen in vesicles or cytosol –> CD4, CD8 T cells.
What is the adaptive immune response of an intracellular microbe in non-phagocytic cell (virus)?
Antigen in cytosol –> CD8 CTLs.
What is the adaptive immune response of a helminth parasite?
Th2 response –> IgE, eosinophils.
What is the effector mechanism of an extracellular microbe (bacteria, viruses)?
Neutralization and phagocytosis.
What is the effector mechanism of an intracellular microbe in phagocytes?
IFN-gamma activates phagocytes; killing of infected cells.
What is the effector mechanism of an intracellular microbe in non-phagocytic cell (virus)?
Killing of infected cells.
What is the effector mechanism of a helminth parasite?
Eosinophil-mediated killing of IgE-coated parasites.
What are the protective functions of the immune response to extracellular bacteria?
- Antibody. 2. Activated macrophages.
What are the protective functions of the immune response to intracellular bacteria?
- T cell-mediated macrophage activation. 2. CTL-mediated killing of infected cells.
What are the protective functions of the immune response to viruses?
- Antibody. 2. CTL-mediated killing of infected cells.
What are the characteristics of memory cells?
Survive even after infection is cleared, more numbers than naive cells, respond more rapidly than naive cells, provide rapid protection against recurrent or persistent infections, goal of vx.
What is the role of memory T cells?
Migrate to tissues, some live in mucosal tissues and skin.
What is the role of memory B cells?
Produce high affinity, often isotype switched, antibodies.
Describe innate immunity to viruses.
Protection against infection via type 1 IFN; eradication of established infection by NK cells destroying infected cells.
Describe adaptive immunity to viruses.
Protection against infection via neutralization of antibodies by B cells; eradication of established infection by CD8 CTLs killing infected cell.
What is the role of antibodies in adaptive immunity to viruses?
Neutralization of viruses to prevent infection; block infectious virus early in course of infection (before entering cells) or after release from infected cells (prevents cell-to-cell spread).
What is the role of CTLs in adaptive immunity to viruses?
Kill infected cells and eradicate reservoirs of established infection; defective T cell immunity leads to reactivation of the virus.
What are examples of antigenic variation that allows for immune evasion by viruses?
Influenza, HIV, and rhinovirus.
How do viruses evade the immune system?
Inhibition of the class I MHC antigen processing pathway.
What are the host adaptations for killing class I MHC negative infected cells?
NK cells.
Describe immune modulators that allow for immune evasion by viruses.
Soluble cytokine receptors may act as decoys and block actions of cytokines (poxviruses); immunosuppressive cytokines (IL-10).
What describes the infection of immune cells?
HIV.
What happens in the case of antigenic drift?
Antigen changes shape.
What happens in the case of antigenic shift?
Genetic change allowing strain jump across animal species.
Describe the adaptive immunity to extracellular microbes by antibodies.
The only way of preventing most infections; high-affinity Ab’s are most effective; isotype switched Ab’s trigger multiple effector mechanisms; long-lived plasma cells provide prolonged protection.
What are the mechanisms by which antibodies work in adaptive immunity against extracellular microbes?
Neutralization, opsonization and Fc receptor-mediated phagocytosis, phagocytosis of C3b-coated bacteria, inflammation, and bacterial lysis.
Describe the role of helper T cells in adaptive immunity to extracellular microbes.
Ab response, macrophage activation for phagocytosis and bacterial killing, and inflammation.
Describe cell-mediated immunity against intracellular microbes.
CD4 T cells: make phagocytes better killers of microbes; CD8 T cells: eliminate the reservoir of infection.
How do CD4 and CD8 cells cooperate in cell-mediated immunity against intracellular microbes?
CD4 T cells help to kill microbes in vesicles of phagocytes via IFN-gamma while CTLs kill microbes that have escaped into the cytoplasm.
Describe Ab responses to bacteria.
Major antigens of many bacteria are polysaccharides, and defense is mediated only by antigens (T-independent); T cell dependent Ab responses to protein antigens are more effective; critical role of the spleen in bacterial clearance.
What is the reason for the development of ‘conjugate vx’?
T cell dependent Ab response to protein antigens.
What are the local injurious effects of anti-bacterial immunity?
Acute inflammation, tissue damage.
Systemic effects of inflammation (fever, metabolic abnormalities) are mediated by what?
Cytokines.
What is a severe effect of anti-bacterial immunity?
Septic shock; caused by cytokines induced by LPS, endotoxins.
What are rare late sequelae?
Immune complex diseases; cross reactive responses against self tissues.
Host responses to fungal infections are provided by what?
Neutrophils and macrophages.
What has a limited role in host defense against fungal infections?
Antibodies.
Describe the role of Th2 responses in defense against helminths.
Eosinophils are better at killing helminths than are other leukocytes; the TH2 response and IgE provide a mechanism for bringing eosinophils to helminths and activating the cells.
Describe purified antigens.
Protective antibody; not effective against microbes that mutate antigenic proteins or hide inside infected cells.
What are plasmid DNA vaccines used for?
Induce effective CTL responses with purified protein antigens.
Describe the efficacy of vaccines.
Vaccines have been useful for generating protective antibodies, but so far, not for generating effective cell-mediated immunity.
Vaccines work best against microbes that:
- Don’t vary their antigens.
- Don’t have animal reservoirs.
- Don’t establish latent infection within host cells.
- Don’t interfere with the host immune response.
The Th2 type response refers to what?
Combined immune response, which include both innate and adaptive components.
Th1 cells fight what?
Viruses, cancer, yeast, and intracellular pneumonia.
Th2 cells fight what?
Normal bacteria, parasites, toxins, and allergens.
Describe the immune response of adaptive immunity to helminths.
Th2 cells –> IL4, IL5 –> IgE, eosinophils.
Describe the immune response of adaptive immunity to Leishmania.
T cells produce IFN gamma for activation of phagocytes.
Describe the immune response of adaptive immunity to malaria.
CD8 T cells –> secretion of cytokines.
Describe the effector mechanism for adaptive immunity to helminths.
Eosinophils kill IgE-coated parasites (form of ADCC).
Describe the effector mechanism for adaptive immunity to Leishmania.
Phagocytes kill parasites living in endosomes.
Describe the effector mechanism for adaptive immunity to malaria.
IFN-gamma, TNF activate macrophages, neutrophils to kill parasites.
